Stereoselective Synthesis of Nicotinamide β-Riboside and Nucleoside Analogues (original) (raw)
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Stereoselective synthesis of nicotinamide β-riboside and nucleoside analogs
Bioorganic & Medicinal Chemistry Letters, 2004
The b-anomers of N-ribofuranosylnicotine-3-carboxamide (b-NAR) and its nicotinic acid analog (b-NaR) were obtained by stereoselective synthesis via glycosylation of the presilylated bases under VorbruggenÕs protocol. A NAR analog, methylated in position 3 of the ribosylic moiety, is also reported. 1 H NMR (300 MHz DMSO-d 6 ): d (ppm) 4.85 (d, J = 3.3 Hz, 2H, H5 0 ), 5.20 (m, 1H, H4 0 ), 6.0 (t, J = 5.6 Hz, 1H, H3 0 ), 6.15 (dd, J = 3.3, 5.8 Hz, 1H, H2 0 ), 7.05 (d, J = 3.6 Hz, 1H, H1 0 ), 7.20-8.15 (m, 15H, arom.), 8.25 (t, J = 7.6 Hz, 1H, H5), 9.0 (d, J = 8.4 Hz, 1H, H4), 9.40 (d, J = 6.6 Hz, 1H, H6), 9.70 (s, 1H, H2); MS (API-ESI) m/z 568.1 [MÀTfO À ]. HPLC: retention time: 3.62 min. Anal. calcd for C 32 H 26 NO 9 AE CF 3 SO 3
Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives
Beilstein Journal of Organic Chemistry
The β-anomeric form of nicotinamide riboside (NR+) is a precursor for nicotinamide adenine dinucleotide (NAD+), a redox cofactor playing a critical role in cell metabolism. Recently, it has been demonstrated that its chloride salt (NR+Cl−) has beneficial effects, and now NR+Cl− is available as a dietary supplement. Syntheses and studies of analogues and derivatives of NR+ are of high importance to unravel the role of NR+ in biochemical processes in living cells and to elaborate the next generation of NR+ derivatives and conjugates with the view of developing novel drug and food supplement candidates. This review provides an overview of the synthetic approaches, the chemical properties, and the structural and functional modifications which have been undertaken on the nicotinoyl riboside scaffold.
beta-1,2,3-Triazolyl-nucleosides as nicotinamide riboside mimics
Nucleosides Nucleotides & Nucleic Acids
The synthesis of a series of pyridine- and piperidine-substituted 1,2,3-triazolides linked to a riboside moiety is described. The presence of a triazolide substituent on the pyridine moiety permitted the facile reduction of the latter under mild hydrogenation conditions. These analogues were modelled as to define their similarity to nicotinamide riboside and quantify their ability to bind NAD-dependent protein deacetylases.
Journal of Medicinal Chemistry, 2007
A new two-step methodology achieves stereoselective synthesis of-nicotinamide riboside and a series of related amide, ester, and acid nucleosides. Compounds were prepared through a triacetylatednicotinate ester nucleoside, via coupling of either ethylnicotinate or phenylnicotinate with 1,2,3,5-tetra-O-acetyl-D-ribofuranose. Nicotinamide riboside, nicotinic acid riboside, O-ethylnicotinate riboside, O-methylnicotinate riboside, and several N-alkyl derivatives increased NAD + concentrations from 1.2-2.7-fold in several mammalian cell lines. These findings establish bioavailability and potent effects of these nucleosides in stimulating the increase of NAD + concentrations in mammalian cells.
Stereoselective Synthesis of β-Glycinamide Ribonucleotide
Molecules
A diastereoselective synthesis of the β-anomer of glycinamide ribonucleotide (β-GAR) has been developed. The synthesis was accomplished in nine steps from D-ribose and occurred in 5% overall yield. The route provided material on the multi-milligram scale. The synthetic β-GAR formed was remarkably resistant to anomerization both in solution and as a solid.
Novel synthetic route to the C-nucleoside, 2-deoxy benzamide riboside
Bioorganic & Medicinal Chemistry Letters, 2012
A novel synthetic procedure has been developed that provides access to D/L-2-deoxy-C-nucleosides from 3,4-epoxytetrahydrofuran in seven steps and in moderate to good yields. The key chemical transformation was the Lewis acid catalysed intramolecular cyclisation reaction of an acetal for which the stereochemical outcome was dependent of the reagents' ratio.
The Synthesis of Ribose and Nucleoside Derivatives
Madridge Journal of Novel Drug Research, 2018
Ribose and nucleoside derivatives are important molecules used as drugs. They are structural subunits of nucleic acids and usually obtained by chemical or enzymatic decomposition of nucleic acid. These derivatives are important organic molecules used in the transport of genetic information in living cells. For example, antiviral drugslike a cyclovir are used to prevent viral replication in infected cells. The importance of synthesis of nucleoside, considering probiotics, is increasing because of medical usage for 50 years for patients with cancer or viral infections. The β-D-ribofuranose form of ribose is normal sugar and forms the backbone of RNA. Phosphorylated ribose derivatives such as ATP play important roles in metabolism. Although this study is concerned with the synthesis of ribose and nucleoside derivatives in literature, novel derivatives and methods for the synthesis of ribose and nucleoside analogues are still needed due to their biological importance in synthetic organic chemistry. This review covers the synthesized ribose and nucleoside analogues in literature reported from 1914 up to this day.
Synthesis of 6′‐Methyl‐2′‐ O ,4′‐ C ‐methylene‐ α ‐L‐ ribofuranosyl‐pyrimidine Nucleosides
ChemistrySelect, 2019
Herein, we report the efficient synthesis of (6'R)-and (6'S)-6'methyl-2'-O,4'-C-methylene-α-L-ribofuranosyl-thymine, and (6'R)-and (6'S)-6'-methyl-2'-O,4'-C-methylene-α-L-ribofuranosyluracil starting from diacetone glucofuranose in overall yields of 6.3, 4.7, 5.4 and 4.0%, respectively. The key step in the synthesis of stereochemically defined 6'-Me-bicyclic-nucleosides is the nucleophilic addition of methyl group at methylene carbon of 4-C-CH 2 OH moiety of the 4-C-tert-butyldiphenylsilyloxymethylated sugar precursor. Thus, the methyl group was added on the aldehyde obtained from Dess-Martin periodinane oxidation of the precursor alcohol employing AlMe 3 in hexane. Both (6'R)and (6'S)-stereoisomers of bicyclic nucleosides T and U were successfully synthesized following Vorbrüggen nucleobase coupling of T and U with triacetylated glycosyl donor obtained from acetolysis of (5R)-and (5 S)-4-C-(tert-butyldiphenylsilyloxymethyl)-5-C-methyl-1,2-O-isopropylidene-3-O-(2-naphthylmethyl)-α-D-xylofuranoses and further cyclization and deprotection of the resulted nucleoside. One of the nucleosides, (6'R)-6'-methyl-2'-O,4'-C-methylene-α-L-ribofuranosyl-uracil has been reported earlier in 1.8% yield, while the present methodology yielded the nucleoside in 5.4% yield. All the synthesized 6'-Me-bicyclic-nucleosides showed no significant anti-viral activity against H1 N1 strain of influenza A virus (A/Puerto Rico/ 8/1934). Experimental procedures including materials, reagents and solvents used for the synthesis of compounds 1, 2, 3 a, 3 b, (5R)-4, (5S)-5, (5R)-6, (5S)-7, 8 ad , 9 ad , 10 ad , 11 ad , 12 ad and 13 ad and their characterization data along with their 1 H and 13 C NMR spectra are given in the supplementary information.
Nicotinamide Riboside Derivatives: Single Crystal Growth and Determination of X-ray Structures
Crystal Growth & Design, 2019
For the first time, the X-ray structure of nicotinamide riboside could be determined. Five nicotinamide riboside (NR) derivatives in their native, thioamide and triacetyl protected form could be crystallized as their chloride and bromide salts. The single crystals were obtained with the help of the vapor diffusion technique. The use of the much slower layering technique for crystallization led to the decomposition of the nicotinamide ribosides yielding the corresponding nicotinamide salts. The torsion angles of the five nicotinamide riboside derivatives were compared with those obtained from the two nicotinamide adenine dinucleotide crystal and the three protein nicotinamide riboside cocrystal structures.